Sacubitril/valsartan augments postprandial plasma concentrations of active GLP-1 when combined with sitagliptin in men
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Nicolai J Wewer Albrechtsen, Peter D Mark, Dijana Terzic, Lasse H Hansen, Ulrik Ø Andersen, Bolette Hartmann, Richard D Carr, Finn Gustafsson, Carolyn F Deacon, Jens J Holst, Jens P Goetze, Peter Plomgaard
CONTEXT: Combined inhibition of neprilysin and dipeptidyl peptidase 4 (DPP-4) has been shown to augment plasma concentrations of glucagon-like peptide-1(GLP-1) in animal models, but whether this occurs in humans is unknown.
OBJECTIVE: To investigate the effects of inhibition of neprilysin by sacubitril/valsartan alone or in combination with a DPP-4 inhibitor (sitagliptin) on plasma concentrations of GLP-1 in healthy men.
DESIGN: Two open-labeled crossover studies were performed in human subjects.
SETTING: General community.
PARTICIPANTS: Nine and 10 healthy young males were included in study 1 and study 2, respectively.
INTERVENTION: Study participants received a standardized meal (34% carbohydrates, 45% fat, 21% protein, total caloric content of 2106kJ) combined with a prior dose of either sacubitril/valsartan (194/206mg) or control in study 1, and in study 2, with a prior dose of sitagliptin (2x100mg, given ∼10 hours apart) either alone or with sacubitril/valsartan (194/206mg).
MAIN OUTCOME MEASURES: Plasma concentrations of total and intact GLP-1.
RESULTS: Sacubitril/valsartan increased postprandial plasma concentrations of total GLP-1 by 67% (tAUC0-240min: 3929±344 vs. 2348±181 min × pmol/L P=0.0023), and increased concentrations of intact GLP-1 plasma concentrations more than sitagliptin alone (tAUC0-240min: 1021±114 vs. 660±80 min × pmol/L, P=0.01). Plasma concentrations of glucose, insulin, and GIP were not significantly (P>0.10) changed upon sacubitril/valsartan treatment.
CONCLUSIONS: Sacubitril/valsartan combined with a DPP-4 inhibitor lead to markedly higher concentrations of intact GLP-1 than DPP-4 inhibition alone, supporting a role for both neprilysin and DPP-4 in the metabolism of GLP-1 in humans, a finding which may have therapeutic implications.
|Tidsskrift||The Journal of clinical endocrinology and metabolism|
|Status||E-pub ahead of print - 10 maj 2019|